Sarilumab for Relapse of Polymyalgia Rheumatica during Glucocorticoid Taper.

BACKGROUND: More than half of patients with polymyalgia rheumatica have a relapse during tapering of glucocorticoid therapy. Previous studies have suggested that interleukin-6 blockade may be clinically useful in the treatment of polymyalgia rheumatica. Sarilumab, a human monoclonal antibody, binds interleukin-6 receptor α and efficiently blocks the interleukin-6 pathway. METHODS: In this phase 3 trial, we randomly assigned patients in a 1:1 ratio to receive 52 weeks of a twice-monthly subcutaneous injection of either sarilumab (at a dose of 200 mg) plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. The primary outcome at 52 weeks was sustained remission, which was defined as the resolution of signs and symptoms of polymyalgia rheumatica by week 12 and sustained normalization of the C-reactive protein level, absence of disease flare, and adherence to the prednisone taper from weeks 12 through 52. RESULTS: A total of 118 patients underwent randomization (60 to receive sarilumab and 58 to receive placebo). At week 52, sustained remission occurred in 28% (17 of 60 patients) in the sarilumab group and in 10% (6 of 58 patients) in the placebo group (difference, 18 percentage points; 95% confidence interval, 4 to 32; P = 0.02). The median cumulative glucocorticoid dose at 52 weeks was significantly lower in the sarilumab group than in the placebo group (777 mg vs. 2044 mg; P<0.001). The most common adverse events with sarilumab as compared with placebo were neutropenia (15% vs. 0%), arthralgia (15% vs. 5%), and diarrhea (12% vs. 2%). More treatment-related discontinuations were observed in the sarilumab group than in the placebo group (12% vs. 7%). CONCLUSIONS: Sarilumab showed significant efficacy in achieving sustained remission and reducing the cumulative glucocorticoid dose in patients with a relapse of polymyalgia rheumatica during glucocorticoid tapering. (Funded by Sanofi and Regeneron Pharmaceuticals; SAPHYR ClinicalTrials.gov number, NCT03600818.).

Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica.

OBJECTIVES: To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). METHODS: A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment. CONCLUSION: These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.

EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice: 2023 update.

OBJECTIVES: To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV). METHODS: A systematic literature review update was performed to retrieve new evidence on ultrasound, MRI, CT and [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnosis, monitoring and outcome prediction in LVV. The task force consisted of 24 physicians, health professionals and patients from 14 countries. The recommendations were updated based on evidence and expert opinion, iterating until voting indicated consensus. The level of agreement was determined by anonymous votes. RESULTS: Three overarching principles and eight recommendations were agreed. Compared to the 2018 version, ultrasound is now recommended as first-line imaging test in all patients with suspected giant cell arteritis, and axillary arteries should be included in the standard examination. As an alternative to ultrasound, cranial and extracranial arteries can be examined by FDG-PET or MRI. For Takayasu arteritis, MRI is the preferred imaging modality; FDG-PET, CT or ultrasound are alternatives. Although imaging is not routinely recommended for follow-up, ultrasound, FDG-PET or MRI may be used for assessing vessel abnormalities in LVV patients with suspected relapse, particularly when laboratory markers of inflammation are unreliable. MR-angiography, CT-angiography or ultrasound may be used for long-term monitoring of structural damage, particularly at sites of preceding vascular inflammation. CONCLUSIONS: The 2023 EULAR recommendations provide up-to-date guidance for the role of imaging in the diagnosis and assessment of patients with LVV.

The provisional OMERACT ultrasonography score for giant cell arteritis.

OBJECTIVES: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties. METHODS: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24. RESULTS: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff 0.37-0.48). CONCLUSION: We developed a provisional OGUS for potential use in clinical trials.

An international survey of current management practices for polymyalgia rheumatica by general practitioners and rheumatologists.

OBJECTIVES: To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment. METHODS: An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group. RESULTS: In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials. CONCLUSION: This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials.

Rituximab versus tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis (R4RA): 16-week outcomes of a stratified, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial.

BACKGROUND: Although targeted biological treatments have transformed the outlook for patients with rheumatoid arthritis, 40% of patients show poor clinical response, which is mechanistically still unexplained. Because more than 50% of patients with rheumatoid arthritis have low or absent CD20 B cells-the target for rituximab-in the main disease tissue (joint synovium), we hypothesised that, in these patients, the IL-6 receptor inhibitor tocilizumab would be more effective. The aim of this trial was to compare the effect of tocilizumab with rituximab in patients with rheumatoid arthritis who had an inadequate response to anti-tumour necrosis factor (TNF) stratified for synovial B-cell status. METHODS: This study was a 48-week, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial (rituximab vs tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis; R4RA) done in 19 centres across five European countries (the UK, Belgium, Italy, Portugal, and Spain). Patients aged 18 years or older who fulfilled the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for rheumatoid arthritis and were eligible for treatment with rituximab therapy according to UK National Institute for Health and Care Excellence guidelines were eligible for inclusion in the trial. To inform balanced stratification, following a baseline synovial biopsy, patients were classified histologically as B-cell poor or rich. Patients were then randomly assigned (1:1) centrally in block sizes of six and four to receive two 1000 mg rituximab infusions at an interval of 2 weeks (rituximab group) or 8 mg/kg tocilizumab infusions at 4-week intervals (tocilizumab group). To enhance the accuracy of the stratification of B-cell poor and B-cell rich patients, baseline synovial biopsies from all participants were subjected to RNA sequencing and reclassified by B-cell molecular signature. The study was powered to test the superiority of tocilizumab over rituximab in the B-cell poor population at 16 weeks. The primary endpoint was defined as a 50% improvement in Clinical Disease Activity Index (CDAI50%) from baseline. The trial is registered on the ISRCTN database, ISRCTN97443826, and EudraCT, 2012-002535-28. FINDINGS: Between Feb 28, 2013, and Jan 17, 2019, 164 patients were classified histologically and were randomly assigned to the rituximab group (83 [51%]) or the tocilizumab group (81 [49%]). In patients histologically classified as B-cell poor, there was no statistically significant difference in CDAI50% between the rituximab group (17 [45%] of 38 patients) and the tocilizumab group (23 [56%] of 41 patients; difference 11% [95% CI -11 to 33], p=0·31). However, in the synovial biopsies classified as B-cell poor with RNA sequencing the tocilizumab group had a significantly higher response rate compared with the rituximab group for CDAI50% (rituximab group 12 [36%] of 33 patients vs tocilizumab group 20 [63%] of 32 patients; difference 26% [2 to 50], p=0·035). Occurrence of adverse events (rituximab group 76 [70%] of 108 patients vs tocilizumab group 94 [80%] of 117 patients; difference 10% [-1 to 21) and serious adverse events (rituximab group 8 [7%] of 108 vs tocilizumab group 12 [10%] of 117; difference 3% [-5 to 10]) were not significantly different between treatment groups. INTERPRETATION: The results suggest that RNA sequencing-based stratification of rheumatoid arthritis synovial tissue showed stronger associations with clinical responses compared with histopathological classification. Additionally, for patients with low or absent B-cell lineage expression signature in synovial tissue tocilizumab is more effective than rituximab. Replication of the results and validation of the RNA sequencing-based classification in independent cohorts is required before making treatment recommendations for clinical practice. FUNDING: Efficacy and Mechanism Evaluation programme from the UK National Institute for Health Research.

Efficacy and safety of mavrilimumab in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial.

OBJECTIVES: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is implicated in pathogenesis of giant cell arteritis. We evaluated the efficacy of the GM-CSF receptor antagonist mavrilimumab in maintaining disease remission. METHODS: This phase 2, double-blind, placebo-controlled trial enrolled patients with biopsy-confirmed or imaging-confirmed giant cell arteritis in 50 centres (North America, Europe, Australia). Active disease within 6 weeks of baseline was required for inclusion. Patients in glucocorticoid-induced remission were randomly assigned (3:2 ratio) to mavrilimumab 150 mg or placebo injected subcutaneously every 2 weeks. Both groups received a 26-week prednisone taper. The primary outcome was time to adjudicated flare by week 26. A prespecified secondary efficacy outcome was sustained remission at week 26 by Kaplan-Meier estimation. Safety was also assessed. RESULTS: Of 42 mavrilimumab recipients, flare occurred in 19% (n=8). Of 28 placebo recipients, flare occurred in 46% (n=13). Median time to flare (primary outcome) was 25.1 weeks in the placebo group, but the median was not reached in the mavrilimumab group (HR 0.38; 95% CI 0.15 to 0.92; p=0.026). Sustained remission at week 26 was 83% for mavrilimumab and 50% for placebo recipients (p=0.0038). Adverse events occurred in 78.6% (n=33) of mavrilimumab and 89.3% (n=25) of placebo recipients. No deaths or vision loss occurred in either group. CONCLUSIONS: Mavrilimumab plus 26 weeks of prednisone was superior to placebo plus 26 weeks of prednisone for time to flare by week 26 and sustained remission in patients with giant cell arteritis. Longer treatment is needed to determine response durability and quantify the glucocorticoid-sparing potential of mavrilimumab. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number: NCT03827018, Europe (EUdraCT number: 2018-001003-36), and Australia (CT-2018-CTN-01 865-1).

New-onset versus relapsing giant cell arteritis treated with tocilizumab: 3-year results from a randomized controlled trial and extension.

OBJECTIVE: Tocilizumab plus prednisone induces sustained glucocorticoid-free remission in patients with GCA. However, its long-term benefits in new-onset vs relapsing disease are uncertain, and the value of weekly vs every-other-week dosing has not been evaluated. METHODS: In Giant-Cell Arteritis Actemra (GiACTA) part 1, patients with new-onset or relapsing GCA received blinded tocilizumab weekly (TCZ QW), tocilizumab every-other-week (TCZ Q2W) or placebo for 52 weeks, with a prednisone taper. In part 2 (open-label), patients were treated at investigator discretion for 104 weeks. In this analysis, patients were evaluated according to their original treatment assignments, and outcomes beyond 52 weeks were assessed. Outcomes of interest included time to first flare and cumulative glucocorticoid exposure over 3 years according to baseline disease status. RESULTS: Part 1 enrolled 250 patients; 215 entered part 2. At baseline, 48% had new-onset disease and 52% had relapsing disease. In patients with new-onset and relapsing disease, the median time to first flare in the TCZ QW group was 577 and 575 days, respectively, vs 479 and 428 days with TCZ Q2W and 179 and 224 days with placebo; the median cumulative glucocorticoid dose was 3068 mg and 2191 mg with TCZ QW, 4080 mg and 2353 mg with TCZ Q2W, and 4639 mg and 6178 mg with placebo. CONCLUSION: TCZ QW delayed the time to flare and reduced the cumulative glucocorticoid dose in patients with relapsing GCA and new-onset GCA. These data support initiating TCZ QW as part of first-line therapy in all patients with active GCA. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01791153.

Ultrasonographic Halo Score in giant cell arteritis: association with intimal hyperplasia and ischaemic sight loss.

OBJECTIVES: We investigated the relationship between the ultrasonographic Halo Score and temporal artery biopsy (TAB) findings in GCA. METHODS: This is a prospective study including 90 patients suspected of having GCA. Ultrasonography of temporal/axillary arteries and a TAB were obtained in all patients at baseline. An experienced pathologist evaluated whether TAB findings were consistent with GCA, and whether transmural inflammation, giant cells and intimal hyperplasia were present. Ultrasonographic Halo Scores were determined. Receiver operating characteristic analysis was performed. RESULTS: Twenty-seven patients had a positive TAB, while 32 patients with a negative TAB received a clinical diagnosis of GCA after 6 months of follow-up. Patients with a positive TAB showed higher Halo Scores than patients with a negative TAB. The presence of intimal hyperplasia in the biopsy, rather than the presence of transmural inflammation or giant cells, was associated with elevated Halo Scores in patients with GCA. The Halo Score discriminated well between TAB-positive patients with and without intimal hyperplasia, as indicated by an area under the curve of 0.82 in the receiver operating characteristic analysis. Patients with a positive TAB and intimal hyperplasia more frequently presented with ocular ischaemia (40%) than the other patients with GCA (13-14%). CONCLUSION: The ultrasonographic Halo Score may help to identify a subset of GCA patients with intimal hyperplasia, a TAB feature associated with ischaemic sight loss.

A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis.

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 × 10-54, per-allele OR = 1.79; and rs9275592, p = 1.14 × 10-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 × 10-10, OR = 1.28; and rs128738, p = 4.60 × 10-9, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis.

Trial of Tocilizumab in Giant-Cell Arteritis.

BACKGROUND: Giant-cell arteritis commonly relapses when glucocorticoids are tapered, and the prolonged use of glucocorticoids is associated with side effects. The effect of the interleukin-6 receptor alpha inhibitor tocilizumab on the rates of relapse during glucocorticoid tapering was studied in patients with giant-cell arteritis. METHODS: In this 1-year trial, we randomly assigned 251 patients, in a 2:1:1:1 ratio, to receive subcutaneous tocilizumab (at a dose of 162 mg) weekly or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. The primary outcome was the rate of sustained glucocorticoid-free remission at week 52 in each tocilizumab group as compared with the rate in the placebo group that underwent the 26-week prednisone taper. The key secondary outcome was the rate of remission in each tocilizumab group as compared with the placebo group that underwent the 52-week prednisone taper. Dosing of prednisone and safety were also assessed. RESULTS: Sustained remission at week 52 occurred in 56% of the patients treated with tocilizumab weekly and in 53% of those treated with tocilizumab every other week, as compared with 14% of those in the placebo group that underwent the 26-week prednisone taper and 18% of those in the placebo group that underwent the 52-week prednisone taper (P<0.001 for the comparisons of either active treatment with placebo). The cumulative median prednisone dose over the 52-week period was 1862 mg in each tocilizumab group, as compared with 3296 mg in the placebo group that underwent the 26-week taper (P<0.001 for both comparisons) and 3818 mg in the placebo group that underwent the 52-week taper (P<0.001 for both comparisons). Serious adverse events occurred in 15% of the patients in the group that received tocilizumab weekly, 14% of those in the group that received tocilizumab every other week, 22% of those in the placebo group that underwent the 26-week taper, and 25% of those in the placebo group that underwent the 52-week taper. Anterior ischemic optic neuropathy developed in one patient in the group that received tocilizumab every other week. CONCLUSIONS: Tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with giant-cell arteritis. Longer follow-up is necessary to determine the durability of remission and safety of tocilizumab. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT01791153 .).

Novel ultrasonographic Halo Score for giant cell arteritis: assessment of diagnostic accuracy and association with ocular ischaemia.

OBJECTIVES: Ultrasound of temporal and axillary arteries may reveal vessel wall inflammation in patients with giant cell arteritis (GCA). We developed a ultrasound scoring system to quantify the extent of vascular inflammation and investigated its diagnostic accuracy and association with clinical factors in GCA. METHODS: This is a prospective study including 89 patients suspected of having GCA, of whom 58 had a confirmed clinical diagnosis of GCA after 6 months follow-up. All patients underwent bilateral ultrasound examination of the three temporal artery (TA) segments and axillary arteries, prior to TA biopsy. The extent of vascular inflammation was quantified by (1) counting the number of TA segments and axillary arteries with a halo and (2) calculating a composite Halo Score that also incorporated the thickness of each halo. RESULTS: Halo counts and Halo Scores showed moderate diagnostic accuracy for a clinical diagnosis of GCA. They correlated positively with systemic inflammation. When compared with the halo count, the Halo Score correlated better with C-reactive protein (CRP) levels and allowed to firmly establish the diagnosis of GCA in more patients. Higher halo counts and Halo Scores were associated with a higher risk of ocular ischaemia. They allowed to identify subgroups of patients with low risk (≤5%) and high risk of ocular ischaemia (>30%). CONCLUSIONS: Ultrasound halo scoring allows to quantify the extent of vascular inflammation in GCA. Extensive vascular inflammation on ultrasound may provide strong diagnostic confirmation and associates with ocular ischaemia in GCA.

2018 Update of the EULAR recommendations for the management of large vessel vasculitis.

BACKGROUND: Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations. METHODS: Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations. RESULTS: Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons. CONCLUSIONS: We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.

Early variation of ultrasound halo sign with treatment and relation with clinical features in patients with giant cell arteritis.

OBJECTIVES: To compare the ultrasound characteristics with clinical features, final diagnosis and outcome; and to evaluate the halo size following glucocorticoid treatment in patients with newly diagnosed GCA. METHODS: Patients with suspected GCA, recruited from an international cohort, had an ultrasound of temporal (TA) and axillary (AX) arteries performed within 7 days of commencing glucocorticoids. We compared differences in clinical features at disease presentation, after 2 weeks and after 6 months, according to the presence or absence of halo sign. We undertook a cross-sectional analysis of the differences in halo thickness using Pearson's correlation coefficient (r) and Analysis of Variance (ANOVA). RESULTS: A total of 345 patients with 6 months follow-up data were included; 226 (65.5%) had a diagnosis of GCA. Jaw claudication and visual symptoms were more frequent in patients with halo sign (P =0.018 and P =0.003, respectively). Physical examination abnormalities were significantly associated with the presence of ipsilateral halo (P <0.05). Stenosis or occlusion on ultrasound failed to contribute to the diagnosis of GCA. During 7 days of glucocorticoid treatment, there was a consistent reduction in halo size in the TA (maximum halo size per patient: r=-0.30, P =0.001; and all halos r=-0.23, P <0.001), but not in the AX (P >0.05). However, the presence of halo at baseline failed to predict future ischaemic events occurring during follow-up. CONCLUSION: In newly diagnosed GCA, TA halo is associated with the presence of ischaemic features and its size decreases following glucocorticoid treatment, supporting its early use as a marker of disease activity, in addition to its diagnostic role.

The impact of disease extent and severity detected by quantitative ultrasound analysis in the diagnosis and outcome of giant cell arteritis.

OBJECTIVES: To develop a quantitative score based on colour duplex sonography (CDS) to predict the diagnosis and outcome of GCA. METHODS: We selected patients with positive CDS and confirmed diagnosis of GCA recruited into the TA Biopsy (TAB) vs Ultrasound in Diagnosis of GCA (TABUL) study and in a validation, independent cohort. We fitted four CDS models including combinations of the following: number and distribution of halos at the TA branches, average and maximum intima-media thickness of TA and axillary arteries. We fitted four clinical/laboratory models. The combined CDS and clinical models were used to develop a score to predict risk of positive TAB and clinical outcome at 6 months. RESULTS: We included 135 GCA patients from TABUL (female: 68%, age 73 (8) years) and 72 patients from the independent cohort (female: 46%, age 75 (7) years). The best-fitting CDS model for TAB used maximum intima-media thickness size and bilaterality of TA and axillary arteries' halos. The best-fitting clinical model included raised inflammatory markers, PMR, headache and ischaemic symptoms. By combining CDS and clinical models we derived a score to compute the probability of a positive TAB. Model discrimination was fair (area under the receiver operating characteristic curve 0.77, 95% CI: 0.68, 0.84). No significant association was found for prediction of clinical outcome at 6 months. CONCLUSION: A quantitative analysis of CDS and clinical characteristics is useful to identify patients with a positive biopsy, supporting the use of CDS as a surrogate tool to replace TAB. No predictive role was found for worse prognosis.

2018 EULAR recommendations for a core data set to support observational research and clinical care in giant cell arteritis.

Giant cell arteritis (GCA) represents the most common form of primary systemic vasculitis and is frequently associated with comorbidities related to the disease itself or induced by the treatment. Systematically collected data on disease course, treatment and outcomes of GCA remain scarce. The aim of this EULAR Task Force was to identify a core set of items which can easily be collected by experienced clinicians, in order to facilitate collaborative research into the course and outcomes of GCA. A multidisciplinary EULAR task force group of 20 experts including rheumatologists, internists, epidemiologists and patient representatives was assembled. During a 1-day meeting, breakout groups discussed items from a previously compiled collection of parameters describing GCA status and disease course. Feedback from breakout groups was further discussed. Final consensus was achieved by means of several rounds of email discussions after the meeting. A three-round Delphi survey was conducted to determine a core set of parameters including the level of agreement. 117 parameters were regarded as relevant. Potential items were subdivided into the following categories: General, demographics, GCA-related signs and symptoms, other medical conditions and treatment. Possible instruments and assessment intervals were proposed for documentation of each item. To facilitate implementation of the recommendations in clinical care and clinical research, a minimum core set of 50 parameters was agreed. This proposed core set intends to ensure that relevant items from different GCA registries and databases can be compared for the dual purposes of facilitating clinical research and improving clinical care.

Identification of an activated neutrophil phenotype in polymyalgia rheumatica during steroid treatment: a potential involvement of immune cell cross-talk.

We have reported the existence of a distinct neutrophil phenotype in giant cell arteritis (GCA) patients arising at week 24 of steroid treatment. In the present study, we investigated whether longitudinal analysis of neutrophil phenotype in patients with polymyalgia rheumatica (PMR) could reveal a novel association with disease status and immune cell cross-talk. Thus, we monitored PMR patient neutrophil phenotype and plasma microvesicle (MV) profiles in blood aliquots collected pre-steroid, and then at weeks 1, 4, 12 and 24 post-steroid treatment.Using flow cytometric and flow chamber analyses, we identified 12-week post-steroid as a pivotal time-point for a marked degree of neutrophil activation, correlating with disease activity. Analyses of plasma MVs indicated elevated AnxA1+ neutrophil-derived vesicles which, in vitro, modulated T-cell reactivity, suggesting distinct neutrophil phenotypic and cross-talk changes at 24 weeks, but not at 12-week post-steroid.Together, these data indicate a clear distinction from GCA patient neutrophil and MV signatures, and provide an opportunity for further investigations on how to 'stratify' PMR patients and monitor their clinical responses through novel use of blood biomarkers.

A probability score to aid the diagnosis of suspected giant cell arteritis.

OBJECTIVES: We propose a GCA probability score intended to help to risk-stratify patients referred by general practitioners with suspected GCA into those with high probability of GCA versus low probability of GCA. In this pilot study we evaluated the diagnostic accuracy of this proposed scoring system. METHODS: A scoring system was proposed based on clinical experience. Retrospective analysis was conducted from clinical notes of consecutive patients presenting to a Fast Track Pathway clinic between August 2016 and August 2017. The GCA Probability Score was calculated for each patient and receiver operating characteristic (ROC) curve plotted. RESULTS: Of 122 consecutive patients, full data were available for calculation of GCA probability score in all patients except one (excluded from this analysis). The area under the ROC curve was 0.953 (95% confidence interval: 0.911, 0.994). The ROC curve showed an optimal cut point of 9.5 out of a possible score of 32. At this cut-point there was a sensitivity of 95.7% and specificity 86.7%, and 88.4% of cases were correctly classified. CONCLUSIONS: The GCA Probability Score is a promising and feasible tool for risk stratification of patients referred by general practitioners with suspected GCA. In a fast track clinic setting this aids exclusion of GCA in low probability cases and confirmation of disease in high probability disease. Refinement and subsequent external validation of this score is required.